Arthritis is a family of diseases resulting in inflammation and pain at body joints and possibly other internal organs. The effects of arthritis can be debilitating to a subject's quality of life; effective treatments for many members of the arthritis-family of diseases are limited and are of varying degrees of effectiveness.
In looking at the spectrum of diseases making up the arthritis family, a small percentage, i.e., approximately 5%, of arthritis patients have rheumatoid arthritis (RA). RA patients often possess certain markers of the disease, i.e., are seropositive for RA factor and exhibit an elevated erythrocyte sedimentation rate and anti-nuclear antibodies. Thus, rheumatoid arthritis is an arthritic condition that can usually be readily diagnosed. Typically, RA patients are treated with non-steroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs), corticosteroids, or newer biologics that block specific hormones involved in the inflammatory process.
Reactive arthritis (ReA), formally considered as yet another type of arthritis, can develop following a microbial infection in an area in the body outside of the affected joint or joints (i.e. a distant infection), such as in the genitourinary or intestinal tract. Known triggering microbes include, e.g., Chlamydia trachomatis, Yersinia enterocolitica, Salmonella, Shigella, Campylobacter, Neisseria, Ureaplasma urealyticum, and Streptococcus pyogenes, to name a few of the most frequently-associated microbes. Most often, the inflamed joint or joints possess no cultivable microbes. In instances in which the genitourinary tract, eyes, skin or muscles are also affected, ReA may be referred to as Reiter's Syndrome.
Another approximately 3-4% of arthritis patients, including reactive arthritis patients, have syndromes such as ankylosing spondylitis and psoriatic arthritis. Ankylosing spondylitis (AS) is a syndrome that mainly affects the spine but can also affect other joints, tendons and ligaments. AS is a painful, progressive, rheumatic disease. In patients suffering from AS, inflammation occurs at the site where certain ligaments or tendons attach to bone (enthesis). This is followed by some erosion of bone at the site of the attachment (enthesopathy). As the inflammation subsides, a healing process takes place and new bone develops. Movement becomes restricted where bone replaces the elastic tissue of ligaments or tendons. Repetition of this inflammatory process leads to further bone formation and the individual bones that make up the backbone, i.e., the vertebrae, often fuse together.
Psoriatic arthritis is another syndrome-type of arthritis that causes pain and swelling in some joints, and scaly skin patches on some areas of the body. It is related to the skin condition psoriasis; its cause is unknown.
The remainder of arthritis patients suffer from osteoarthritis (OA) and other arthropathies. Approximately 50% of all patients suffering from arthritic disease possess osteoarthritis, a type of arthritis that is associated with a breakdown of cartilage in body joints. This disease causes pain and difficulty in bone movement. Associated pain can also result from involvement of muscles and other tissues, i.e., tendons and ligaments, at diseased joints. Typical therapies for the treatment of OA include the administration of painkillers, NSAIDs and corticosteroids. Although not to be bound or limited by theory, it is the inventors' belief that reactive or enthesopathic arthritis is a precursor to osteoarthritis in a majority of patients diagnosed with osteoarthritis. In such cases, it is believed that following an initial triggering infection, a low level microbial infection persists, but often goes unnoticed or undetected for an extended period of time, often several years, until it has caused enough joint destruction to be classified as osteoarthritis.
The diagnosis of reactive arthritis by clinicians can be extremely difficult, as no overall agreement exists within the medical community on general guidelines setting forth diagnostic criteria for ReA. Further, patients are often unaware of the occurrence of the triggering infection, e.g., in the case of an often-asymptomatic infection such as genital Chlamydia trachomatis. Moreover, patients suffering from ReA are seronegative for any blood markers, further complicating its proper diagnosis.
Symptoms associated with ReA may include one or more of the following: joint discomfort, skin and mucous membrane symptoms, gastrointestinal manifestations, and ocular lesions. The most common symptom is joint discomfort, where the most commonly affected joints are those of the lower extremities, such as the knee, ankle, and joints of the foot. Additional symptoms may include fatigue, malaise, fever, weight loss, urethritis and prostatitis in males, and cervicitis or salpingitis in females.
As is evident from the above, reactive arthritis is a serious condition that can be extremely painful. Long term follow-up studies have indicated that 20-70% of patients with ReA later suffer from joint discomfort or other symptoms (Toivanen, A. and Toivanen, P., Best Practice & Research Clinical Rheumatology, Vol 18, No. 5, p. 689-703 (2004). Commonly employed treatments for ReA include the administering of NSAIDs, disease-modifying anti-rheumatic drugs, and corticosteroids. The administration of such drugs is typically aimed at managing the pain and inflammation associated with ReA.
Several studies have examined the use of antibiotics in the treatment of reactive arthritis (Sieper, J., Braun, J., British Journal of Rheumatology 1998; 37:717-720 and references cited therein). Most of the studies to date have employed the use of a single antibiotic such as tetracycline, lymecycline (Lauhio, A., et al., Arthritis Rheum 1001: 34:6-16), or ciprofloxacin (Toivanen A., et al., Clin Exp Rheumatol 1993; 11:301-7). However, none of these studies has concluded an advantage or has recommended long-term treatment of ReA with antibiotics. Rather, the majority of studies have found antibiotics to be of limited or of no use in the treatment of ReA. (Sieper, J., Braun, J., ibid).
Yet another painful inflammatory condition is bursitis. Bursitis is inflammation of a bursa—a small, fluid-filled sac lined with synovial tissue. There are over one hundred fifty bursae in the human body. These bursae lubricate and cushion pressure points between the bones and the tendons, and their function is to facilitate movement of tendons and muscles over bony prominences. Bursitis may be caused by excessive frictional forces, trauma, systemic disease such as rheumatoid arthritis or gout, or infection. Many times, its cause is unknown.
Treatment of bursitis generally includes resting and immobilizing the affected area, applying ice to reduce swelling, and taking non-steroidal anti-inflammatory drugs to reduce pain and inflammation. In certain instances, a corticosteroid is administered to relieve inflammation; oftentimes, relief is immediate. In instances in which the bursitis is caused by infection, a single antibiotic may be administered. Unfortunately, with the currently available treatment regimes, recurrent flare-ups are common, and can be extremely frustrating as well as painful. Over a long term, bursitis can result in loss of joint use and chronic pain syndrome. Thus, the long-term adverse effects of bursitis can range from chronic pain to crippling disability.
In sum, currently known therapies for the treatment of diagnosed reactive arthritis, osteoarthritis, and bursitis have been of a limited, if any, well-accepted degree of success. Based upon the on-going research focused on reactive arthritis, it can be seen that there is a need for an effective therapy for the treatment of reactive arthritis and osteoarthritis (herein considered a consequence of reactive arthritis). There also exists a need for an effective therapy for treating other inflammatory conditions such as bursitis. In particular, there is a need for compositions and treatments effective to significantly ameliorate or ideally, eliminate, joint pain, tenderness, stiffness, and fatigue associated with one or more of the above conditions. The present invention meets this need.